The Urinary System

Urinary System Organs

•   Kidneys are major excretory organs

•   Urinary bladder is the temporary storage reservoir for urine

•   Ureters transport urine from the kidneys to the bladder

•   Urethra transports urine out of the body

Kidney Functions

•   Removal of toxins, metabolic wastes, and excess ions from the blood

•   Regulation of blood volume, chemical composition, and pH

Kidney Functions

•   Gluconeogenesis during prolonged fasting

•   Endocrine functions

•    Renin: regulation of blood pressure and kidney function

•    Erythropoietin: regulation of RBC production

•   Activation of vitamin D

 Kidney Anatomy

•   Retroperitoneal, in the superior lumbar region

•   Right kidney is lower than the left

•   Convex lateral surface, concave medial surface

•   Renal hilum leads to the renal sinus

•   Ureters, renal blood vessels, lymphatics, and nerves enter and exit at the hilum

Kidney Anatomy

•   Layers of supportive tissue

1.Renal fascia

•   The anchoring outer layer of dense fibrous connective tissue

2.Perirenal fat capsule

•   A fatty cushion

3.Fibrous capsule

•   Prevents spread of infection to kidney

Internal Anatomy

•   Renal cortex

•    A granular superficial region

•   Renal medulla

•    The cone-shaped medullary (renal) pyramids separated by renal columns

•   Lobe

•    A medullary pyramid and its surrounding cortical tissue

Internal Anatomy

•   Papilla

•    Tip of pyramid; releases urine into minor calyx

•   Renal pelvis

•    The funnel-shaped tube within the renal sinus

Internal Anatomy

•   Major calyces

•    The branching channels of the renal pelvis that

•   Collect urine from minor calyces

•   Empty urine into the pelvis

•   Urine flows from the pelvis to ureter

Blood and Nerve Supply

•   Renal arteries deliver ~ ¹/₄ (1200 ml) of cardiac output to the kidneys each minute

•   Arterial flow into and venous flow out of the kidneys follow similar paths

•   Nerve supply is via sympathetic fibers from the renal plexus

Nephrons

•   Structural and functional units that form urine

•   ~1 million per kidney

•   Two main parts

1.Glomerulus: a tuft of capillaries

2.Renal tubule: begins as cup-shaped glomerular (Bowman’s) capsule surrounding the glomerulus

Nephrons

•   Renal corpuscle

•    Glomerulus + its glomerular capsule

•   Fenestrated glomerular endothelium

•    Allows filtrate to pass from plasma into the glomerular capsule

Renal Tubule

•   Glomerular capsule

•   Parietal layer: simple squamous epithelium

•   Visceral layer: branching epithelial podocytes

•    Extensions terminate in foot processes that cling to basement membrane

•    Filtration slits allow filtrate to pass into the capsular space

Renal Tubule

•   Proximal convoluted tubule (PCT)

•    Cuboidal cells with dense microvilli and large mitochondria

•    Functions in reabsorption and secretion

•    Confined to the cortex

Renal Tubule

•   Loop of Henle with descending and ascending limbs

•    Thin segment usually in descending limb

•   Simple squamous epithelium

•   Freely permeable to water

•    Thick segment of ascending limb

•   Cuboidal to columnar cells

Renal Tubule

•   Distal convoluted tubule (DCT)

•    Cuboidal cells with very few microvilli

•    Function more in secretion than reabsorption

•    Confined to the cortex

Collecting Ducts

•   Receive filtrate from many nephrons

•   Fuse together to deliver urine through papillae into minor calyces

Collecting Ducts

•   Cell types

•    Intercalated cells

•   Cuboidal cells with microvilli

•   Function in maintaining the acid-base balance of the body

Collecting Ducts

•    Principal cells

•   Cuboidal cells without microvilli

•   Help maintain the body’s water and salt balance

Nephrons

•   Cortical nephrons—85% of nephrons; almost entirely in the cortex

•   Juxtamedullary nephrons

•    Long loops of Henle deeply invade the medulla

•    Extensive thin segments

•    Important in the production of concentrated urine

Nephron Capillary Beds

1.Glomerulus

•    Afferent arteriole ® glomerulus ® efferent arteriole

•    Specialized for filtration

•    Blood pressure is high because

•   Afferent arterioles are smaller in diameter than efferent arterioles

•   Arterioles are high-resistance vessels

Nephron Capillary Beds

2.Peritubular capillaries

•    Low-pressure, porous capillaries adapted for absorption

•    Arise from efferent arterioles

•    Cling to adjacent renal tubules in cortex

•    Empty into venules

Nephron Capillary Beds

3.Vasa recta

•    Long vessels parallel to long loops of Henle

•    Arise from efferent arterioles of juxtamedullary nephrons

•    Function information of concentrated urine

Vascular Resistance in Microcirculation

•   High resistance in afferent and efferent arterioles

•    Causes blood pressure to decline from ~95 mm Hg to ~8 mm Hg in kidneys

Vascular Resistance in Microcirculation

•   Resistance in afferent arterioles

•    Protects glomeruli from fluctuations in systemic blood pressure

•   Resistance in efferent arterioles

•    Reinforces high glomerular pressure

•    Reduces hydrostatic pressure in peritubular capillaries

Juxtaglomerular Apparatus (JGA)

•   One per nephron

•   Important in regulation of filtrate formation and blood pressure

•   Involves modified portions of the

•    Distal portion of the ascending limb of the loop of Henle

•    Afferent (sometimes efferent) arteriole

Juxtaglomerular Apparatus (JGA)

•   Granular cells (juxtaglomerular, or JG cells)

•    Enlarged, smooth muscle cells of arteriole

•    Secretory granules contain renin

•    Act as mechanoreceptors that sense blood pressure

Juxtaglomerular Apparatus (JGA)

•   Macula densa

•    Tall, closely packed cells of the ascending limb

•    Act as chemoreceptors that sense NaCl content of filtrate

•   Extraglomerular mesangial cells

•    Interconnected with gap junctions

•    May pass signals between macula densa and granular cells

Filtration Membrane

•   Porous membrane between the blood and the capsular space

•   Consists of

1.  Fenestrated endothelium of the glomerular capillaries

2.  Visceral membrane of the glomerular capsule (podocytes with foot processes and filtration slits)

3.  Gel-like basement membrane (fused basal laminae of the two other layers)

Filtration Membrane

•   Allows passage of water and solutes smaller than most plasma proteins

•    Fenestrations prevent filtration of blood cells

•    Negatively charged basement membrane repels large anions such as plasma proteins

•    Slit diaphragms also help to repel macromolecules

Filtration Membrane

•   Glomerular mesangial cells

•    Engulf and degrade macromolecules

•    Can contract to change the total surface area available for filtration

Kidney Physiology: Mechanisms of Urine Formation

•   The kidneys filter the body’s entire plasma volume 60 times each day

•   Filtrate

•    Blood plasma minus proteins

•   Urine

•    <1% of total filtrate

•    Contains metabolic wastes and unneeded substances

Mechanisms of Urine Formation

1.Glomerular filtration

2.Tubular reabsorption

•    Returns all glucose and amino acids, 99% of water, salt, and other components to the blood

3.Tubular secretion

•    Reverse of reabsoprtion: selective addition to urine

Glomerular Filtration

•   Passive mechanical process driven by hydrostatic pressure

•   The glomerulus is a very efficient filter because

•     Its filtration membrane is very permeable and it has a large surface area

•     Glomerular blood pressure is higher (55 mm Hg) than other capillaries

•   Molecules >5 nm are not filtered (e.g., plasma proteins) and function to maintain colloid osmotic pressure of the blood

Net Filtration Pressure (NFP)

•   The pressure responsible for filtrate formation (10 mm Hg)

Net Filtration Pressure (NFP)

•   Determined by

•    Glomerular hydrostatic pressure (HP_g) the chief force

•    Two opposing forces:

•   Colloid osmotic pressure of glomerular blood (OP_g)

•   Capsular hydrostatic pressure (HP_c)

NFP = HP_g – (OP_g + HP_c)

Glomerular Filtration Rate (GFR)

•   Volume of filtrate formed per minute by the kidneys (120–125 ml/min)

•   Governed by (and directly proportional to)

•    Total surface area available for filtration

•    Filtration membrane permeability

•    NFP

Regulation of Glomerular Filtration

•   GFR is tightly controlled by two types of mechanisms

•   Intrinsic controls (renal autoregulation)

•    Act locally within the kidney

•   Extrinsic controls

•    Nervous and endocrine mechanisms that maintain blood pressure, but affect kidney function

Intrinsic Controls

•   Maintains a nearly constant GFR when MAP is in the range of 80–180 mm Hg

•   Two types of renal autoregulation

•    Myogenic mechanism (Chapter 19)

•    Tubuloglomerular feedback mechanism, which senses changes in the juxtaglomerular apparatus

Intrinsic Controls: Myogenic Mechanism

•   ­ BP ® constriction of afferent arterioles

•    Helps maintain normal GFR

•    Protects glomeruli from damaging high BP

•   ¯ BP ® dilation of afferent arterioles

•    Helps maintain normal GFR

Intrinsic Controls: Tubuloglomerular Feedback Mechanism

•   Flow-dependent mechanism directed by the macula densa cells

•   If GFR increases, filtrate flow rate increases in the tubule

•   Filtrate NaCl concentration will be high because of insufficient time for reabsorption

Intrinsic Controls: Tubuloglomerular Feedback Mechanism

•   Macula densa cells of the JGA respond to ­NaCl by releasing a vasoconstricting chemical that acts on the afferent arteriole ® ¯ GFR

•   The opposite occurs if GFR decreases.

Extrinsic Controls: Sympathetic Nervous System

•   Under normal conditions at rest

•    Renal blood vessels are dilated

•    Renal autoregulation mechanisms prevail

Extrinsic Controls: Sympathetic Nervous System

•   Under extreme stress

•    Norepinephrine is released by the sympathetic nervous system

•    Epinephrine is released by the adrenal medulla

•    Both cause constriction of afferent arterioles, inhibiting filtration and triggering the release of renin

Extrinsic Controls: Renin-Angiotensin Mechanism

•   Triggered when the granular cells of the JGA release renin

angiotensinogen (a plasma globulin)

                          resin ® 

                                    angiotensin I

angiotensin converting
enzyme (ACE) ®

                                   angiotensin II

Effects of Angiotensin II

1.Constricts arteriolar smooth muscle, causing MAP to rise 

2.Stimulates the reabsorption of Na⁺

•    Acts directly on the renal tubules

•    Triggers adrenal cortex to release aldosterone

3.Stimulates the hypothalamus to release ADH and activates the thirst center

Effects of Angiotensin II

4.Constricts efferent arterioles, decreasing peritubular capillary hydrostatic pressure and increasing fluid reabsorption

5.Causes glomerular mesangial cells to contract, decreasing the surface area available for filtration

Extrinsic Controls: Renin-Angiotensin Mechanism

•   Triggers for renin release by granular cells

•    Reduced stretch of granular cells (MAP below 80 mm Hg)

•    Stimulation of the granular cells by activated macula densa cells

•    Direct stimulation of granular cells via b1-adrenergic receptors by renal nerves

Other Factors Affecting GRF

•   Prostaglandin E₂

•    Vasodilator that counteracts vasoconstriction by norepinephrine and angiotensin II

•    Prevents renal damage when peripheral resistance is increased

Other Factors Affecting GRF

•   Intrarenal angiotensin II

•    Reinforces the effects of hormonal angiotensin II

•   Adenosine

•    A vasoconstrictor of renal vasculature

 

Tubular Reabsorption

•   A selective transepithelial process

•    All organic nutrients are reabsorbed

•    Water and ion reabsorption are hormonally regulated

•   Includes active and passive process

•   Two routes

•    Transcellular

•    Paracellular

Tubular Reabsorption

•   Transcellular route

•    Luminal membranes of tubule cells

•    Cytosol of tubule cells

•    Basolateral membranes of tubule cells

•    Endothelium of peritubular capillaries

Tubular Reabsorption

•   Paracellular route

•    Between cells

•    Limited to water movement and reabsorption of Ca²⁺, Mg²⁺, K⁺, and some Na⁺ in the PCT where tight junctions are leaky

Sodium Reabsorption

•   Na⁺ (most abundant cation in filtrate)

•    Primary active transport out of the tubule cell by
 Na⁺-K⁺ ATPase in the basolateral membrane

•    Na⁺ passes in through the luminal membrane by secondary active transport or facilitated diffusion mechanisms

Sodium Reabsorption

•   Low hydrostatic pressure and high osmotic pressure in the peritubular capillaries

•   Promotes bulk flow of water and solutes (including Na⁺)

Reabsorption of Nutrients, Water, and Ions

•   Na+ reabsorption provides the energy and the means for reabsorbing most other substances

•   Organic nutrients are reabsorbed by secondary active transport

•    Transport maximum (Tm) reflects the number of carriers in the renal tubules available

•    When the carriers are saturated, excess of that substance is excreted

Reabsorption of Nutrients, Water, and Ions

•   Water is reabsorbed by osmosis (obligatory water reabsorption), aided by water-filled pores called aquaporins

•   Cations and fat-soluble substances follow by diffusion

Reabsorptive Capabilities of Renal Tubules and Collecting Ducts

•   PCT

•    Site of most reabsorption

•   65% of Na⁺ and water

•   All nutrients

•   Ions

•   Small proteins

Reabsorptive Capabilities of Renal Tubules and Collecting Ducts

•   Loop of Henle

•    Descending limb: H₂O 

•    Ascending limb: Na⁺, K⁺, Cl^-

Reabsorptive Capabilities of Renal Tubules and Collecting Ducts

•   DCT and collecting duct

•    Reabsorption is hormonally regulated

•   Ca²⁺ (PTH)

•   Water (ADH)

•   Na⁺ (aldosterone and ANP)

Reabsorptive Capabilities of Renal Tubules and Collecting Ducts

•   Mechanism of aldosterone

•    Targets collecting ducts (principal cells) and distal DCT

•    Promotes synthesis of luminal Na⁺ and K⁺ channels

•    Promotes synthesis of basolateral Na⁺-K⁺ ATPases

Tubular Secretion

•   Reabsorption in reverse

•    K⁺, H⁺, NH₄⁺, creatinine, and organic acids move from peritubular capillaries or tubule cells into filtrate

•   Disposes of substances that are bound to plasma proteins

Tubular Secretion

•   Eliminates undesirable substances that have been passively reabsorbed (e.g., urea and uric acid)

•   Rids the body of excess K⁺

•   Controls blood pH by altering amounts of H⁺ or HCO₃^– in urine

Regulation of Urine Concentration and Volume

•   Osmolality

•    Number of solute particles in 1 kg of H₂O

•    Reflects ability to cause osmosis

Regulation of Urine Concentration and Volume

•   Osmolality of body fluids

•    Expressed in milliosmols (mOsm)

•    The kidneys maintain osmolality of plasma at ~300 mOsm, using countercurrent mechanisms

Countercurrent Mechanism

•   Occurs when fluid flows in opposite directions in two adjacent segments of the same tube

•    Filtrate flow in the loop of Henle (countercurrent multiplier)

•    Blood flow in the vasa recta (countercurrent exchanger)

Countercurrent Mechanism

•   Role of countercurrent mechanisms

•    Establish and maintain an osmotic gradient (300 mOsm to 1200 mOsm) from renal cortex through the medulla

•    Allow the kidneys to vary urine concentration

Countercurrent Multiplier: Loop of Henle

•   Descending limb

•    Freely permeable to H₂O, which passes out of the filtrate into the hyperosmotic medullary interstitial fluid

•    Filtrate osmolality increases to ~1200 mOsm

Countercurrent Multiplier: Loop of Henle

•   Ascending limb

•    Impermeable to H₂O

•    Selectively permeable to solutes

•   Na⁺ and Cl^– are passively reabsorbed in the thin segment, actively reabsorbed in the thick segment

•    Filtrate osmolality decreases to 100 mOsm

Urea Recycling

•   Urea moves between the collecting ducts and the loop of Henle

•    Secreted into filtrate by facilitated diffusion in the ascending thin segment

•    Reabsorbed by facilitated diffusion in the collecting ducts deep in the medulla

•   Contributes to the high osmolality in the medulla

Countercurrent Exchanger: Vasa Recta

•   The vasa recta

•    Maintain the osmotic gradient

•    Deliver blood to the medullary tissues

•    Protect the medullary osmotic gradient by preventing rapid removal of salt, and by removing reabsorbed H₂O

Formation of Dilute Urine

•   Filtrate is diluted in the ascending loop of Henle

•   In the absence of ADH, dilute filtrate continues into the renal pelvis as dilute urine

•   Na⁺ and other ions may be selectively removed in the DCT and collecting duct, decreasing osmolality to as low as 50 mOsm

Formation of Concentrated Urine

•   Depends on the medullary osmotic gradient and ADH

•   ADH triggers reabsorption of H₂O in the collecting ducts

•   Facultative water reabsorption occurs in the presence of ADH so that 99% of H₂O in filtrate is reabsorbed

Diuretics

•   Chemicals that enhance the urinary output

•    Osmotic diuretics: substances not reabsorbed, (e.g., high glucose in a diabetic patient)

•    ADH inhibitors such as alcohol

•    Substances that inhibit Na⁺ reabsorption and obligatory H₂O reabsorption such as caffeine and many drugs

Renal Clearance

•   Volume of plasma cleared of a particular substance in a given time

•   Renal clearance tests are used to

•    Determine GFR

•    Detect glomerular damage

•    Follow the progress of renal disease

Renal Clearance

RC = UV/P

RC = renal clearance rate (ml/min)

U = concentration (mg/ml) of the substance in urine

V = flow rate of urine formation (ml/min)

P = concentration of the same substance in plasma

Renal Clearance

•   For any substance freely filtered and neither reabsorbed nor secreted by the kidneys (e.g., insulin),

RC = GFR = 125 ml/min

•   If RC < 125 ml/min, the substance is reabsorbed

•   If RC = 0, the substance is completely reabsorbed

•   If RC > 125 ml/min, the substance is secreted (most drug metabolites)

Physical Characteristics of Urine

•   Color and transparency

•    Clear, pale to deep yellow (due to urochrome)

•    Drugs, vitamin supplements, and diet can alter the color

•    Cloudy urine may indicate a urinary tract infection

Physical Characteristics of Urine

•   Odor

•    Slightly aromatic when fresh

•    Develops ammonia odor upon standing

•    May be altered by some drugs and vegetables

Physical Characteristics of Urine

•   pH

•    Slightly acidic (~pH 6, with a range of 4.5 to 8.0)

•    Diet, prolonged vomiting, or urinary tract infections may alter pH

•   Specific gravity

•    1.001 to 1.035, dependent on solute concentration

Chemical Composition of Urine

•   95% water and 5% solutes

•   Nitrogenous wastes: urea, uric acid, and creatinine

•   Other normal solutes

•    Na⁺, K⁺, PO₄^3–, and SO₄^2–,

•    Ca²⁺, Mg²⁺ and HCO₃^–

•   Abnormally high concentrations of any constituent may indicate pathology

Ureters

•   Convey urine from kidneys to bladder

•   Retroperitoneal

•   Enter the base of the bladder through the posterior wall

•    As bladder pressure increases, distal ends of the ureters close, preventing backflow of urine

Ureters

•   Three layers of wall of ureter

1.Lining of transitional epithelium

2.Smooth muscle muscularis

•   Contracts in response to stretch

3.Outer adventitia of fibrous connective tissue

Renal Calculi

•   Kidney stones form in renal pelvis

•    Crystallized calcium, magnesium, or uric acid salts

•   Larger stones block ureter, cause pressure and pain in kidneys

•   May be due to chronic bacterial infection, urine retention, ­Ca²⁺ in blood, ­pH of urine

Urinary Bladder

•   Muscular sac for temporary storage of urine

•   Retroperitoneal, on pelvic floor posterior to pubic symphysis

•    Males—prostate gland surrounds the neck inferiorly

•    Females—anterior to the vagina and uterus

Urinary Bladder

•   Trigone

•    Smooth triangular area outlined by the openings for the ureters and the urethra

•    Infections tend to persist in this region

Urinary Bladder

•   Layers of the bladder wall 

1.Transitional epithelial mucosa

2.Thick detrusor muscle (three layers of smooth muscle)

3.Fibrous adventitia (peritoneum on superior surface only)

Urinary Bladder

•   Collapses when empty; rugae appear

•   Expands and rises superiorly during filling without significant rise in internal pressure

Urethra

•   Muscular tube

•    Lining epithelium

•   Mostly pseudostratified columnar epithelium, except

•   Transitional epithelium near bladder

•   Stratified squamous epithelium near external urethral orifice

Urethra

•   Sphincters

•    Internal urethral sphincter

•   Involuntary (smooth muscle) at bladder-urethra junction

•   Contracts to open

•    External urethral sphincter

•   Voluntary (skeletal) muscle surrounding the urethra as it passes through the pelvic floor

Urethra

•   Female urethra (3–4 cm):

•    Tightly bound to the anterior vaginal wall

•    External urethral orifice is anterior to the vaginal opening, posterior to the clitoris

Urethra

•   Male urethra

•    Carries semen and urine

•    Three named regions

1.Prostatic urethra (2.5 cm)—within prostate gland

2.Membranous urethra (2 cm)—passes through the urogenital diaphragm

3.Spongy urethra (15 cm)—passes through the penis and opens via the external urethral orifice

Micturition

•   Urination or voiding

•   Three simultaneous events

1.Contraction of detrusor muscle by ANS

2.Opening of internal urethral sphincter by ANS

3.Opening of external urethral sphincter by somatic nervous system

Micturition

•   Reflexive urination (urination in infants)

•    Distension of bladder activates stretch receptors

•    Excitation of parasympathetic neurons in reflex center in sacral region of spinal cord

•    Contraction of the detrusor muscle

•    Contraction (opening) of internal sphincter

•    Inhibition of somatic pathways to external sphincter, allowing its relaxation (opening)

Micturition

•   Pontine control centers mature between ages 2 and 3

1.  Pontine storage center inhibits micturition:

•   Inhibits parasympathetic pathways

•   Excites sympathetic and somatic efferent pathways

2.  Pontine micturition center promotes micturition:

•   Excites parasympathetic pathways

•   Inhibits sympathetic and somatic efferent pathways

Developmental Aspects

•   Three sets of embryonic kidneys forming succession

1.Pronephros degenerates but pronephric duct persists

2.Mesonephros claims this duct and it becomes the mesonephric duct

3.Metanephros develops by the fifth week, develops into adult kidneys and ascends

Developmental Aspects

•   Metanephros develops as ureteric buds that induce mesoderm of urogenital ridge to form nephrons

•     Distal ends of ureteric buds form renal pelves, calyces, and collecting ducts

•     Proximal ends become ureters

•   Kidneys excrete urine into amniotic fluid by the third month

•   Cloaca subdivides into rectum, anal canal, and urogenital sinus

Developmental Aspects

•   Frequent micturition in infants due to small bladders and less-concentrated urine

•   Incontinence is normal in infants: control of the voluntary urethral sphincter develops with the nervous system

•   E. coli bacteria account for 80% of all urinary tract infections

•   Streptococcal infections may cause long-term renal damage

•   Sexually transmitted diseases can also inflame the urinary tract